Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation.

INTRODUCTION: Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. METHODS: LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. RESULTS: The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. CONCLUSIONS: While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Lung transplantation in the septuagenarian can be successfully performed though long-term results impacted by diseases of aging.

BACKGROUND: Advanced age is considered a risk factor for lung transplantation (LTX). We sought to evaluate the long-term outcomes of LTX in the septuagenarian. METHODS: LTX recipients in the UNOS transplant registry (May 1, 2005-June 12, 2020) were stratified into 18-59, 60-69, and > = 70 years of age. Recipient and transplant characteristics were evaluated for survival, cause of death (COD), length of stay (LOS), and complications. A Kaplan-Meier analysis examined long-term survival for all patients stratified by age, specifically looking at cause of death. RESULTS: A total of 27 632 recipients were identified. As recipients aged, we found a decrease in proportion of cystic fibrosis and an increase in restrictive disease while obstructive disease peaked in the 60-69yo cohort (P < .001). Septuagenarians had higher rates of single LTX, male gender, and white race (P < .001). Older recipients had significantly longer donor recovery distances traveled with paradoxical shorter ischemic times, shorter hospital LOS and were transplanted at higher volume centers. There was no difference with in-hospital mortality among groups (P = .5). Acute rejection during initial hospitalization, rejection within 1 year, and post-transplant dialysis incidence decreased with age. Graft failure was a common COD in younger patients while malignancy and cardio/cerebrovascular diseases were common COD in > = 70yo. CONCLUSION: Select septuagenarian LTX candidates may be safely transplanted with relatively few complications. Immunosenescence and conditions of the aged are likely contributing factors to the decreased rejection and graft failure observations. Septuagenarians should not be excluded from LTX consideration based solely on age. Transplantation in septuagenarians should only be done in very selected patients (screened for malignancies and atherosclerotic disease) and these recipients should be carefully followed after transplantation because of these risk factors.

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis.

INTRODUCTION: Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. METHODS: MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. RESULTS: A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. DISCUSSION: CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Association of Preoperative Pneumonia With Postsurgical Morbidity and Mortality in Children.

BACKGROUND: Pneumonia is a common lower respiratory tract infection (LRI) and the leading cause of pediatric hospitalization in the United States. Given its frequency, children with pneumonia may require surgery during their hospital course. This poses serious anesthetic and surgical challenges because preoperative pulmonary status is among the most important risk factors for postoperative complications. Although recent adult data indicated that preoperative pneumonia was associated with poor surgical outcomes, comparable data in children are lacking. Therefore, our objective was to investigate the association of preoperative pneumonia with postoperative mortality and morbidity in children. METHODS: Using the National Surgical Quality Improvement Program database, we assembled a retrospective cohort of children (<18 years) who underwent inpatient surgery between 2012 and 2015. Our primary outcome was the time to all-cause 30-day postoperative mortality that we evaluated using Cox proportional hazards regression models. For the secondary outcomes, including 30-day postoperative morbidity events, we used Fine-Gray models to account for competing risk by mortality. We also evaluated the association of preoperative pneumonia with duration of postoperative mechanical ventilation and postoperative hospital length of stay. We used propensity score weighting methods to adjust for potential confounding factors, whose distributions differ across the pneumonia groups. RESULTS: Among 153,242 children who underwent inpatient surgery, 0.7% (n = 867) had preoperative pneumonia. Compared with those without preoperative pneumonia, children with preoperative pneumonia had a higher risk of mortality throughout the 30-day postoperative period (hazard ratio [HR], 4.10; 95% confidence intervals [CI], 2.42-6.97; P < .001). Although not statistically significant, children with preoperative pneumonia were twice as likely to develop cardiovascular complications compared to children without preoperative pneumonia (HR, 2.10; 95% CI, 1.17-3.75; P = .012). Furthermore, children with preoperative pneumonia had longer duration of postoperative ventilation (incidence rate ratio, 1.47; 95% CI, 1.26-1.71; P < .001). Finally, children with preoperative pneumonia were estimated to be 56% less likely to be discharged within the 30 days following surgery, compared to children without preoperative pneumonia (HR, 0.44; 95% CI, 0.40-0.47; P < .001). CONCLUSIONS: Preoperative pneumonia was strongly associated with increased incidence of postoperative mortality and complications in children. Clinicians should make concerted efforts to screen for preoperative pneumonia and consider whether proceeding with surgery is the most expedient course of action. Our findings may be helpful in preoperative discussions with parents of children with preoperative pneumonia for risk stratification and postoperative resource allocation purposes.

Attained Functional Status Moderates Survival Outcomes of Return to Work After Lung Transplantation.

BACKGROUND: Returning to work is a desirable outcome of lung transplantation that is selective on attained functional status. Survival implications of post-transplant employment are unclear. METHODS: The United Network for Organ Sharing registry was queried for first-time lung transplants performed from May 2005 to March 2015 in patients ages 18-64. Attainment of normal functional status post-transplant, defined as a 100 % score on the Karnofsky Performance Scale (KPS), was examined as moderating 5-year survival outcomes of work resumption, using Cox proportional hazards models. Supplemental analysis examined attainment of forced expiratory volume in 1 s (FEV1) ≥80 % predicted as moderating survival implications of post-transplant employment. RESULTS: Of 10,066 patients, 1824 (18 %) returned to work, while 9078 contributed follow-up data on functional status. Multivariable analysis demonstrated a protective effect of work resumption among patients who did not attain normal functional status before returning to work (HR = 0.62; 95 % CI = 0.51, 0.76; p < 0.001). This association was attenuated among transplant recipients who reached 100 % KPS while still unemployed (p < 0.001). Similarly, post-transplant survival was favorably associated with 5-year survival among patients who did not attain at least 80 % predicted FEV1 before returning to work (HR = 0.71; 95 % CI = 0.59, 0.86; p < 0.001). CONCLUSIONS: Early return to work after lung transplantation may benefit patients experiencing mild functional limitations. Timing the resumption of employment to coincide with attainment of maximal functional status around 1 year post transplant should be considered.

Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients.

INTRODUCTION: Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. METHODS: UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age ≥ 18 years) first-time LTx recipients diagnosed with CF. RESULTS: The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of ≤200, 201-300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (≤16.5 kg/m(2)). CONCLUSIONS: Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF.

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

BACKGROUND: Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. METHODS: The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. RESULTS: Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. CONCLUSIONS: Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

Eucapnic Voluntary Hyperventilation to Detect Exercise-Induced Bronchoconstriction in Cystic Fibrosis.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) has not been well studied in cystic fibrosis (CF), and eucapnic voluntary hyperventilation (EVH) testing has not been used as an objective assessment of EIB in CF to date. METHODS: A prospective cohort pilot study was completed where standard EVH testing was completed by 10 CF patients with forced expiratory volume in 1 s (FEV1) ≥70% of predicted. All patients also completed a cardiopulmonary exercise test (CPET) with pre- and post-CPET spirometry as a comparative method of detecting EIB. RESULTS: No adverse events occurred with EVH testing. A total of 20% (2/10) patients were diagnosed with EIB by means of EVH. Both patients had clinical symptoms consistent with EIB. No patient had a CPET-based exercise challenge consistent with EIB. CONCLUSIONS: EVH testing was safe and effective in the objective assessment for EIB in patients with CF who had well-preserved lung function. It may be a more sensitive method of detecting EIB then exercise challenge.

Pulmonary hypertension in cystic fibrosis with advanced lung disease.

RATIONALE: The impact of pulmonary hypertension (PH) on survival in cystic fibrosis (CF) remains unclear. OBJECTIVES: To determine the influence of PH on survival in the CF population. METHODS: The United Network for Organ Sharing database was queried from 1987 to 2013 to identify first-time lung transplant candidates who were tracked from wait list entry date until death or censoring to determine influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure greater than or equal to 25 mm Hg and severe greater than or equal to 35 mm Hg. MEASUREMENTS AND MAIN RESULTS: Of 2,781 CF patients, 2,100 were used for univariate analysis, 764 for Kaplan-Meier survival function, 687 for multivariate Cox models, and 576 and 132 for matching on the propensity of mild PH and severe PH, respectively. Univariate Cox analysis found significant differences in survival for mild PH (hazard ratio [HR], 1.747; 95% confidence interval [CI], 1.387-2.201; P < 0.001) and severe PH (HR, 2.299; 95% CI, 1.639-3.225; P < 0.001). Further assessment by multivariate Cox models identified significant risk for death associated with mild PH (HR, 1.757; 95% CI, 1.367-2.258; P < 0.001) and severe PH (HR, 2.284; 95% CI, 1.596-3.268; P < 0.001). Cox regression stratified on matched pairs of PH cases and control subjects confirmed the risk for death for mild PH (HR, 1.919; 95% CI, 1.290-2.85; P = 0.001) and severe PH (HR, 4.167; 95% CI, 1.709-10.157; P = 0.002). CONCLUSIONS: The manifestation of PH is associated with significantly increased risk for death in CF patients with advanced lung disease.

To induce or not to induce: a 21st century evaluation of lung transplant immunosuppression's effect on survival.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in lung transplant recipients remains unclear. We sought to evaluate the effect of contemporary induction immunosuppression agents in lung transplant recipients' survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing registry from 2001 to 2012 for adult, deceased donor lung transplants who received no antibody-based induction (NONE) or the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin, or antithymocyte globulin (INDUCED). Kaplan-Meier estimates of the survival and Cox proportional hazards models assessed differences in overall survival between the INDUCED and NONE groups; logistic regression models assessed differences in survival and rejection (TR1Y). RESULTS: There were 23 951 lung transplants performed with 12 858 meeting the inclusion criteria; 5713 (44%) were INDUCED. Of INDUCED agents, 62% were basiliximab and 14% alemtuzumab. Being INDUCED significantly increased overall survival (p < 0.0001). Median INDUCED survival was 71.3 months (confidence interval [CI]: 65.7-75.5) as compared with 63.2 months (CI: 60.1-65.9). Of INDUCED, both basiliximab and alemtuzumab had higher median survival times at 75.1 months (CI: 68.6-81.3) and 75.5 months (CI: 63.5-∞), respectively. There was less TR1Y in INDUCED patients (37%), as compared to NONE (42%; p < 0.0001). CONCLUSION: In a contemporary analysis of lung transplant recipients, induction immunosuppression has a significantly positive effect on survival.

A contemporary analysis of induction immunosuppression in pediatric lung transplant recipients.

There is an increasing trend in the use of induction immunosuppression in children undergoing lung transplantation (LTx). To evaluate the effect of this practice on survival, the United Network for Organ Sharing (UNOS) was queried from 1987 to 2012, restricting analysis to transplant patients 6-17 years old from 2001 to 2012, who received no induction (NONE) or induction (INDUCED) with the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin (ALG), or antithymocyte globulin (ATG). Of 23 951 lung transplants, 330 met inclusion criteria with 177 (54%) being INDUCED. Of the INDUCED agents, 121 (68%) were basiliximab, 3 (2%) alemtuzumab, and 53 (30%) ALG/ATG/thymoglobulin. The mean patient age was 13.6 (SD = 3.2) and 14 (SD = 3.0) years for the INDUCED and NONE groups, respectively. The median survival in the INDUCED group was 77.4 months (95% CI: 46.1, 125.6) compared with 50.8 months (95% CI: 42.9, 61.3) for the NONE (log-rank P-value = 0.3601). The most common cause of death was due to allograft failure or pulmonary complications with only one patient dying from post-transplant lymphoproliferative disorder. The estimated hazard ratio for INDUCED versus NONE was 0.859 (95% CI: 0.620, 1.191; P = 0.3618); there were no significant confounders or effect modifiers among the demographic and clinical variables. In conclusion, antibody-based induction immunosuppression with contemporary agents had a trend toward a protective, but not statistically significant, effect in 6- to 17-year-old patients.

Extracorporeal membrane oxygenation and retransplantation in lung transplantation: an analysis of the UNOS registry.

BACKGROUND: Despite limited organ availability, extracorporeal membrane oxygenation (ECMO) and retransplantation are becoming more commonplace. METHODS: Using the United Network for Organ Sharing (UNOS) database, we evaluated survival of patients treated with ECMO before lung transplantation and undergoing retransplantation. A query identified cadaveric recipients from 2001 to 2012 over the age of 6 years. RESULTS: Of 15,772 lung recipients, 15 583 never received ECMO, whereas 189 did. Mean age was 52.1 ± 14.4 versus 46.8 ± 16.5 years for non-ECMO and ECMO groups, respectively (p < 0.0001). Using Kaplan-Meier method, there were survival differences between ECMO and non-ECMO groups (p < 0.0001) and first-time transplants with and without ECMO to retransplants with and without ECMO (p < 0.0001). The proportional hazards model identified higher risk with ECMO use in idiopathic pulmonary fibrosis (hazard ratio [HR] 1.09; 95 % confidence interval (CI), 1.02-1.17; p = 0.014) and retransplants (HR 1.77; 95 % CI, 1.55-2.03; p < 0.0001). CONCLUSIONS: Survival for retransplantation was similar to ECMO as a primary option with significant mortality associated with ECMO use in patients with idiopathic pulmonary fibrosis and retransplants.

Polysomnographic differences associated with pulmonary hypertension in patients with advanced lung disease due to cystic fibrosis.

BACKGROUND: Pulmonary hypertension (PH) commonly occurs in patients with cystic fibrosis (CF), but there is no current data regarding alterations of sleep in patients with PH. METHODS: A single-center, retrospective review was performed in patients with advanced lung disease due to CF who completed both nocturnal polysomnography and right heart catheterization (RHC) from January 2010 to June 2013. For statistical analysis, two-tailed unpaired t tests and Pearson correlation coefficient analysis were performed after normal distribution was confirmed. RESULTS: A total of 18 consecutive CF patients were enrolled with RHC identifying PH in 56 % (10/18) of patients. The PH group had significantly lower mean sleep efficiency (72 ± 4 vs. 87 ± 3 %, p = 0.01), significantly higher ETCO(2) levels (54.5 ± 2.2 vs. 43.8 ± 3.0 mmHg, p = 0.01) on capnography, and significantly lower PO(2) (53.8 ± 3.1 vs. 65.5 ± 3.9 mmHg, p = 0.03) on capillary blood gas. Correlations with poor sleep efficiency included mean PAP (r = - 0.55, p = 0.01), systolic PAP (r = -0.5, p = 0.03), ETCO(2) (r = - 0.53, p = 0.02), and PO(2)) (r = 0.62, p = 0.01); ETCO(2) with systolic PAP (r = 0.47, p = 0.04) and PCO(2) (r = - 0.57, p = 0.01); and PO(2) to 6-min walk distance (r = 0.55, p = 0.02). CONCLUSIONS: We found significant differences in sleep efficiency and gas exchange associated with PH in CF patients with advanced lung disease.

The Role of Cystic Fibrosis Transmembrane Conductance Regulator Modulators After Liver Transplantation in Persons With Cystic Fibrosis.

Despite advances in treatment for cystic fibrosis (CF), liver disease remains a major contributor to morbidity and mortality for persons with CF. Therefore, liver transplantation may be considered in end-stage CF-related liver disease. We present a young patient with CF who underwent solo liver transplantation and has successfully restarted on elexacaftor/tezacaftor/ivacaftor without significant pulmonary or hepatic complications after transplant.

Preventive service utilization among adults with cystic fibrosis covered by private insurance is comparable to the general population.

BACKGROUND: As the life expectancy of the cystic fibrosis (CF) population is lengthening with modulator therapies, diligent age-appropriate screening and preventive care are increasingly vital for long-term health and wellbeing. METHODS: We performed a retrospective analysis comparing rates of receiving age- and sex-appropriate preventive services by commercially insured adult people with CF (PwCF) and adults without CF from the general population (GP) via the Truven Health MarketScan database (2012-2018). RESULTS: We captured 25,369 adults with CF and 488,534 adults from the GP in the United States. Comparing these groups, we found that 43% versus 39% received an annual preventive visit, 28% versus 28% were screened for chlamydia, 38% versus 37% received pap smears every 3 years (21-29-year-old females), 33% versus 31% received pap smears every 5 years (30-64-year-old females), 55% versus 44% received mammograms, 23% versus 21% received colonoscopies, and 21% versus 20% received dyslipidemia screening (all screening rates expressed per 100 person-years). In age-stratified analysis, 18-27-year-old PwCF had a lower rate of annual preventive visits compared to adults in the same age group of the GP (27% versus 42%). CONCLUSIONS: We discovered a comparable-to-superior rate of preventive service utilization in adults with CF relative to the GP, except in young adulthood from 18-27 years. Our findings establish the importance of meeting the primary care needs of adults with CF and call for development of strategies to improve preventive service delivery to young adults.

Reduction of lipid-laden macrophage index after laparoscopic Nissen fundoplication in cystic fibrosis patients after lung transplantation.

BACKGROUND: Lipid-laden macrophage (LLM) index could be potentially useful in assessing gastroesophageal (GE) reflux and aspiration after lung transplantation (LT) in patients with cystic fibrosis (CF). METHODS: A retrospective review of CF patients undergoing LT and/or laparoscopic Nissen fundoplication (LNF) from January 1, 2009, to December 31, 2011, was performed. RESULTS: Seventeen CF patients (nine women), mean (± SD) age 27.9 ± 7.5 yr, underwent LT with mean (± SD) pre-transplant FEV(1) of 20.9 ± 5.0% predicted. Seventy percentage (12/17) of patients underwent LNF without complications within 1-2 wk of LT. After LT, but prior to antireflux surgery, there was no significant difference in the mean (± SD) baseline LLM index (154 ± 41 vs. 146 ± 51, p = NS) between patients who were to undergo LNF and patients who did not. After LNF, a significant reduction in the mean (± SD) LLM index occurred following the procedure (154 ± 41-74 ± 54, p < 0.0001) while each patient reported resolution of symptoms of GE reflux, whereas 40% (2/5) undergoing only medical treatment reported resolution of symptoms. CONCLUSIONS: Significant reduction in the LLM index occurred after LNF in CF patients after LT that correlated with resolution of clinical symptoms of GE reflux.

Surveillance transbronchial biopsies in infant lung and heart-lung transplant recipients.

There are limited published data on surveillance TBB for the identification of allograft rejection in infants after lung or heart-lung transplantation. We performed a retrospective review of children under one yr of age who underwent lung or heart-lung transplant at our institution. Since 2005, four infants were transplanted (three heart-lung and one lung). The mean age (±s.d.) at the time of transplant was 5.5 ± 2.4 (range 3-8) months. A total of 16 surveillance TBB procedures were completed in both inpatient and outpatient settings, with a range of 3-7 performed per patient. A minimum of five acceptable tissue pieces with expanded alveoli were obtained in 81% (13/16) of TBB procedures and a minimum of three pieces in 88% (14/16). There was no evidence of acute allograft rejection in 88% (14/16) of TBB procedures. One TBB procedure yielded two tissue specimens demonstrating A2 acute allograft rejection. One TBB procedure failed to yield tissue with sufficient alveoli. Additionally, B-grade assessment identified B0 in 50% (8/16), B1R in 12% (2/16), and BX (ungradeable or insufficient sample) in 38% (6/16) of biopsy procedures, respectively. In conclusion, TBB may be safely performed as an inpatient and outpatient procedure in infant lung and heart-lung transplant recipients and may provide adequate tissue for detecting acute allograft rejection and small airway inflammation.

Gram-negative infection and bronchiectasis in lung transplant recipients with bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) after lung transplantation manifests as a gradual decline in forced expiratory volume in 1 second. Bronchiectasis is often seen but occurs at variable rates with the underlying pathogenesis being unclear. OBJECTIVE: We completed a study to determine whether lower airway infection with gram-negative bacilli was associated with the development of bronchiectasis in lung transplant recipients with BOS. METHODS: A retrospective review of 17 lung transplant recipients (age: 28 ± 7 years, range: 13 to 40 years) in a patient population transplanted for cystic fibrosis (CF) 82% (14/17), bronchiolitis obliterans 12% (2/17), and sarcoidosis 6% (1/17) was completed. Each patient completed pulmonary function testing and underwent annual computed tomographic imaging of the chest for surveillance posttransplant at a single transplant center. RESULTS: Bronchiectasis was present in 70% (12/17) of patients whereas 94% (16/17) of patients had varying severity of BOS: 1 (n = 7), 2 (n = 3), and 3 (n = 6). All 12 patients with bronchiectasis had an allograft gram-negative rod infection and 92% (11/12) of them had BOS. CONCLUSIONS: The presence of bronchiectasis in lung transplant recipients with BOS was associated with a gram-negative bacterial airway infection of the allograft in a small cohort of predominately lung transplant recipients with CF.

Novel and Engaging Teaching Method for Pulmonary Physiology.

BACKGROUND: Pulmonary physiology is a challenging, necessary component of pediatric pulmonary fellowship education. Our pediatric pulmonology fellowship program provided this education utilizing a flipped classroom approach but satisfaction with the method was declining. Evidence suggests that adult learners benefit from an engaging lecture method, but no evidence exists to compare the flipped classroom approach to the engaging lecture approach for pulmonary physiology education. OBJECTIVE: To develop the most effective physiology curriculum for pediatric pulmonary fellows by comparing the flipped classroom approach to an engaging lecture method. METHODS: Five physiology teaching sessions were assigned to the flipped classroom method and 5 to the engaging lecture style. Anonymous surveys assessing satisfaction, utilizing a five-point Likert scale, were completed by fellows at the end of each session. An unpaired t-test was used to compare responses. RESULTS: Seven pediatric pulmonary fellows enrolled in the study. The average attendance per session was 5 fellows. There was no significant difference in fellows' perceived understanding of the assigned physiology topic prior to the flipped classroom versus engaging lecture sessions. Fellows' perceived understanding of the topics improved after both session types, with significantly more improvement after the engaging lecture sessions. Fellows also reported that engaging lecture sessions were more useful and improved their test-taking confidence. They were more likely to recommend engaging lecture sessions to future pulmonary fellows. CONCLUSIONS: Pediatric pulmonary fellows benefited from the use of the engaging lecture style for physiology education.

Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes. METHODS: We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included. RESULTS: Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7). CONCLUSIONS: CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.